42 results on '"Hiya Banerjee"'
Search Results
2. LEDGF/p75 Overexpression Attenuates Oxidative Stress-Induced Necrosis and Upregulates the Oxidoreductase ERP57/PDIA3/GRP58 in Prostate Cancer.
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Anamika Basu, Christina K Cajigas-Du Ross, Leslimar Rios-Colon, Melanie Mediavilla-Varela, Tracy R Daniels-Wells, Lai Sum Leoh, Heather Rojas, Hiya Banerjee, Shannalee R Martinez, Stephanny Acevedo-Martinez, and Carlos A Casiano
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Medicine ,Science - Abstract
Prostate cancer (PCa) mortality is driven by highly aggressive tumors characterized by metastasis and resistance to therapy, and this aggressiveness is mediated by numerous factors, including activation of stress survival pathways in the pro-inflammatory tumor microenvironment. LEDGF/p75, also known as the DFS70 autoantigen, is a stress transcription co-activator implicated in cancer, HIV-AIDS, and autoimmunity. This protein is targeted by autoantibodies in certain subsets of patients with PCa and inflammatory conditions, as well as in some apparently healthy individuals. LEDGF/p75 is overexpressed in PCa and other cancers, and promotes resistance to chemotherapy-induced cell death via the transactivation of survival proteins. We report in this study that overexpression of LEDGF/p75 in PCa cells attenuates oxidative stress-induced necrosis but not staurosporine-induced apoptosis. This finding was consistent with the observation that while LEDGF/p75 was robustly cleaved in apoptotic cells into a p65 fragment that lacks stress survival activity, it remained relatively intact in necrotic cells. Overexpression of LEDGF/p75 in PCa cells led to the upregulation of transcript and protein levels of the thiol-oxidoreductase ERp57 (also known as GRP58 and PDIA3), whereas its depletion led to ERp57 transcript downregulation. Chromatin immunoprecipitation and transcription reporter assays showed LEDGF/p75 binding to and transactivating the ERp57 promoter, respectively. Immunohistochemical analysis revealed significantly elevated co-expression of these two proteins in clinical prostate tumor tissues. Our results suggest that LEDGF/p75 is not an inhibitor of apoptosis but rather an antagonist of oxidative stress-induced necrosis, and that its overexpression in PCa leads to ERp57 upregulation. These findings are of significance in clarifying the role of the LEDGF/p75 stress survival pathway in PCa.
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- 2016
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3. Expression of the stress response oncoprotein LEDGF/p75 in human cancer: a study of 21 tumor types.
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Anamika Basu, Heather Rojas, Hiya Banerjee, Irena B Cabrera, Kayla Y Perez, Marino De León, and Carlos A Casiano
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Medicine ,Science - Abstract
Oxidative stress-modulated signaling pathways have been implicated in carcinogenesis and therapy resistance. The lens epithelium derived growth factor p75 (LEDGF/p75) is a transcription co-activator that promotes resistance to stress-induced cell death. This protein has been implicated in inflammatory and autoimmune conditions, HIV-AIDS, and cancer. Although LEDGF/p75 is emerging as a stress survival oncoprotein, there is scarce information on its expression in human tumors. The present study was performed to evaluate its expression in a comprehensive panel of human cancers. Transcript expression was examined in the Oncomine cancer gene microarray database and in a TissueScan Cancer Survey Panel quantitative polymerase chain reaction (Q-PCR) array. Protein expression was assessed by immunohistochemistry (IHC) in cancer tissue microarrays (TMAs) containing 1735 tissues representing single or replicate cores from 1220 individual cases (985 tumor and 235 normal tissues). A total of 21 major cancer types were analyzed. Analysis of LEDGF/p75 transcript expression in Oncomine datasets revealed significant upregulation (tumor vs. normal) in 15 out of 17 tumor types. The TissueScan Cancer Q-PCR array revealed significantly elevated LEDGF/p75 transcript expression in prostate, colon, thyroid, and breast cancers. IHC analysis of TMAs revealed significant increased levels of LEDGF/p75 protein in prostate, colon, thyroid, liver and uterine tumors, relative to corresponding normal tissues. Elevated transcript or protein expression of LEDGF/p75 was observed in several tumor types. These results further establish LEDGF/p75 as a cancer-related protein, and provide a rationale for ongoing studies aimed at understanding the clinical significance of its expression in specific human cancers.
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- 2012
- Full Text
- View/download PDF
4. Supplementary Tables S1-7 from Clinical Features Associated with Outcomes and Biomarker Analysis of Dabrafenib plus Trametinib Treatment in Patients with BRAF-Mutant Melanoma Brain Metastases
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Michael A. Davies, Georgina V. Long, John M. Kirkwood, Richard A. Scolyer, Lisa H. Butterfield, Jean-Jacques Grob, Caroline Robert, Philippe Saiag, Peter M. Ferguson, Peter A. Johansson, Hansol Lee, Ismael A. Vergara, Hiya Banerjee, Brindha Shivalingam, Nduka M. Amankulor, Johnathan A. Engh, Hussein Tawbi, and James S. Wilmott
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Supplementary Table S1. Representativeness of study participants Supplementary Table S2. Analysis of the intracranial response duration in the COMBI-MB trial. Supplementary Table S3. Analysis of overall survival in the COMBI-MB trial. Supplementary Table S4. Baseline clinical features of the COMBI-BRV trial. Supplementary Table S5. Gene expression score (SingScore) and multiplex immunohistochemical results. Supplementary Table S6. Summary statistics of the linear mixed models utilized to assess the association between protein/pathway expression/score and biopsy sites. Supplementary Table S7. Mutation annotated file of exome sequencing from melanoma biopsies.
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- 2023
5. Data from Clinical Features Associated with Outcomes and Biomarker Analysis of Dabrafenib plus Trametinib Treatment in Patients with BRAF-Mutant Melanoma Brain Metastases
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Michael A. Davies, Georgina V. Long, John M. Kirkwood, Richard A. Scolyer, Lisa H. Butterfield, Jean-Jacques Grob, Caroline Robert, Philippe Saiag, Peter M. Ferguson, Peter A. Johansson, Hansol Lee, Ismael A. Vergara, Hiya Banerjee, Brindha Shivalingam, Nduka M. Amankulor, Johnathan A. Engh, Hussein Tawbi, and James S. Wilmott
- Abstract
Purpose:This study aimed to identify baseline clinical features associated with the outcomes of patients enrolled in the COMBI-MB phase II study of dabrafenib and trametinib treatment in patients with V600 BRAF-mutant metastatic melanoma with melanoma brain metastases (MBM). Exploratory biomarker analysis was also conducted as part of the synergistic COMBI-BRV trial (BRV116521), to identify molecular and immunologic changes associated with dabrafenib in MBMs and extracranial metastases (ECM).Patients and Methods:Post hoc analysis was performed for baseline features of patients (n = 125) enrolled in COMBI-MB. Analyses were performed to identify baseline clinical features associated with intracranial response rate (ICRR), progression-free survival (PFS), and overall survival (OS).Exploratory biomarker analysis was performed on biospecimen collected in the COMBI-BRV trial in which patients with BRAF-mutant, resectable MBM were treated with dabrafenib for 10 to 14 days prior to craniotomy. Accessible ECM were resected or biopsied at the time of craniotomy. Biospecimens underwent molecular and immunologic profiling for comparative analyses.Results:In COMBI-MB baseline treatment with corticosteroids was independently associated with lower ICRR [39% vs. 63%; OR, 0.323; 95 % confidence interval (CI), 0.105–0.996; P = 0.049] and shorter PFS (HR, 1.93; 95% CI, 1.06–3.51; P = 0.031). Additional significant associations identified in the multivariate analysis were improved PFS in patients with a BRAFV600E genotype (HR, 0.565; 95% CI, 0.321–0.996; P = 0.048) and improved OS in patients with Eastern Cooperative Oncology Group 0 (HR, 0.44; 95% CI, 0.25–0.78; P = 0.005).Conclusions:Corticosteroid treatment was associated with reduced ICRR and PFS in COMBI-MB, similar to results with immunotherapy for MBMs. Baseline corticosteroid treatment is a key factor to consider in MBM patient management and clinical trial design/interpretation.
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- 2023
6. Supplementary Figure S1 from Clinical Features Associated with Outcomes and Biomarker Analysis of Dabrafenib plus Trametinib Treatment in Patients with BRAF-Mutant Melanoma Brain Metastases
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Michael A. Davies, Georgina V. Long, John M. Kirkwood, Richard A. Scolyer, Lisa H. Butterfield, Jean-Jacques Grob, Caroline Robert, Philippe Saiag, Peter M. Ferguson, Peter A. Johansson, Hansol Lee, Ismael A. Vergara, Hiya Banerjee, Brindha Shivalingam, Nduka M. Amankulor, Johnathan A. Engh, Hussein Tawbi, and James S. Wilmott
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Gene expression of major signalling pathways and multiplex immunohistochemical comparison of markers between timepoints and tumor sites. A) Gene expression of related oncogenic signalling pathways between treatment timepoints and site, B) Estimated mean difference of proteins and pathways between biopsy categories (95% confidence interval for the estimated mean difference is depicted as a segment), C) Multiplex immunohistochemical staining for key intracellular signalling proteins, D) Changes in immune intratumoral immune cell densities between treatment timepoints and site, E and F) Multiplex immunohistochemical staining depicted marked decrease in immune cell densities EDT in PT4 (steroid treated). PRE, collected prior to treatment; EDT, collected early during treatment (i.e., after 10-14 days of dabrafenib). MBM, melanoma brain metastasis; ECM, extracranial metastasis. PT, patient.
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- 2023
7. Table S3 from Pazopanib Exposure Relationship with Clinical Efficacy and Safety in the Adjuvant Treatment of Advanced Renal Cell Carcinoma
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Robert J. Motzer, Paola Aimone, Hiya Banerjee, Guillaume Baneyx, Mohamed Elmeliegy, Paul Russo, Christian Doehn, Naomi B. Haas, Frede Donskov, and Cora N. Sternberg
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Baseline patient characteristics and variables used in population PK analysis
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- 2023
8. Figure S1 from Pazopanib Exposure Relationship with Clinical Efficacy and Safety in the Adjuvant Treatment of Advanced Renal Cell Carcinoma
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Robert J. Motzer, Paola Aimone, Hiya Banerjee, Guillaume Baneyx, Mohamed Elmeliegy, Paul Russo, Christian Doehn, Naomi B. Haas, Frede Donskov, and Cora N. Sternberg
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Prediction-corrected visual predictive checks of early (A) and late (B) Ctrough in study PROTECT
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- 2023
9. Data from Pazopanib Exposure Relationship with Clinical Efficacy and Safety in the Adjuvant Treatment of Advanced Renal Cell Carcinoma
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Robert J. Motzer, Paola Aimone, Hiya Banerjee, Guillaume Baneyx, Mohamed Elmeliegy, Paul Russo, Christian Doehn, Naomi B. Haas, Frede Donskov, and Cora N. Sternberg
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Purpose: PROTECT, a phase III, randomized, placebo-controlled study, evaluated pazopanib efficacy and safety in the adjuvant renal cell carcinoma setting. The relationship between pazopanib exposure (Ctrough) and efficacy and safety was evaluated.Patients and Methods: Evaluable steady-state blood trough concentrations were collected from 311 patients at week 3 or 5 (early Ctrough) and 250 patients at week 16 or 20 (late Ctrough). Pazopanib pharmacokinetic (PK) data were analyzed via a population model approach. Relationship between Ctrough or dose intensity and disease-free survival (DFS) was explored via Kaplan–Meier and multivariate analysis. Adverse events (AE) and AE-related treatment discontinuation proportions were summarized by Ctrough quartiles.Results: Most (>90%) patients with early or late Ctrough data started on 600 mg. Mean early and late Ctrough overlapped across dose levels. Patients with higher early Ctrough quartiles achieved longer DFS (adjusted HR, 0.58; 95% confidence interval, 0.42–0.82; P = 0.002). Patients achieving early or late Ctrough >20.5 μg/mL had significantly longer DFS: not estimable (NE) versus 29.5 months, P = 0.006, and NE versus 29.9 months, P = 0.008, respectively. Dose intensity up to week 8 did not correlate with DFS, consistent with population PK model–based simulations showing overlapping pazopanib exposure with 600 and 800 mg doses. The proportion of AE-related treatment discontinuation and grade 3/4 AEs, with the exception of hypertension, was not correlated to Ctrough.Conclusions: In the adjuvant setting, higher pazopanib Ctrough was associated with improved DFS and did not increase treatment discontinuations or grade 3/4 AEs, with the exception of hypertension. Clin Cancer Res; 24(13); 3005–13. ©2018 AACR.See related commentary by Rini, p. 2979
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- 2023
10. PROTECT Study Investigators from Pazopanib Exposure Relationship with Clinical Efficacy and Safety in the Adjuvant Treatment of Advanced Renal Cell Carcinoma
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Robert J. Motzer, Paola Aimone, Hiya Banerjee, Guillaume Baneyx, Mohamed Elmeliegy, Paul Russo, Christian Doehn, Naomi B. Haas, Frede Donskov, and Cora N. Sternberg
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List of PROTECT Study investigators
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- 2023
11. Clinical features associated with outcomes and biomarker analysis of dabrafenib plus trametinib treatment in patients with BRAF-mutant melanoma brain metastases
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James S. Wilmott, Hussein Tawbi, Johnathan A. Engh, Nduka M. Amankulor, Brindha Shivalingam, Hiya Banerjee, Ismael A. Vergara, Hansol Lee, Peter A. Johansson, Peter M. Ferguson, Philippe Saiag, Caroline Robert, Jean-Jacques Grob, Lisa H. Butterfield, Richard A. Scolyer, John M. Kirkwood, Georgina V. Long, and Michael A. Davies
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Cancer Research ,Oncology - Abstract
Purpose: This study aimed to identify baseline clinical features associated with the outcomes of patients enrolled in the COMBI-MB phase II study of dabrafenib and trametinib treatment in patients with V600 BRAF-mutant metastatic melanoma with melanoma brain metastases (MBM). Exploratory biomarker analysis was also conducted as part of the synergistic COMBI-BRV trial (BRV116521), to identify molecular and immunologic changes associated with dabrafenib in MBMs and extracranial metastases (ECM). Patients and Methods: Post hoc analysis was performed for baseline features of patients (n = 125) enrolled in COMBI-MB. Analyses were performed to identify baseline clinical features associated with intracranial response rate (ICRR), progression-free survival (PFS), and overall survival (OS). Exploratory biomarker analysis was performed on biospecimen collected in the COMBI-BRV trial in which patients with BRAF-mutant, resectable MBM were treated with dabrafenib for 10 to 14 days prior to craniotomy. Accessible ECM were resected or biopsied at the time of craniotomy. Biospecimens underwent molecular and immunologic profiling for comparative analyses. Results: In COMBI-MB baseline treatment with corticosteroids was independently associated with lower ICRR [39% vs. 63%; OR, 0.323; 95 % confidence interval (CI), 0.105–0.996; P = 0.049] and shorter PFS (HR, 1.93; 95% CI, 1.06–3.51; P = 0.031). Additional significant associations identified in the multivariate analysis were improved PFS in patients with a BRAFV600E genotype (HR, 0.565; 95% CI, 0.321–0.996; P = 0.048) and improved OS in patients with Eastern Cooperative Oncology Group 0 (HR, 0.44; 95% CI, 0.25–0.78; P = 0.005). Conclusions: Corticosteroid treatment was associated with reduced ICRR and PFS in COMBI-MB, similar to results with immunotherapy for MBMs. Baseline corticosteroid treatment is a key factor to consider in MBM patient management and clinical trial design/interpretation.
- Published
- 2022
12. Pyrexia in patients treated with dabrafenib plus trametinib across clinical trials in BRAF-mutant cancers
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Reinhard Dummer, Georgina V. Long, Alexander M. Menzies, Mike Lau, Keith T. Flaherty, Caroline Robert, Hiya Banerjee, Hussein Abdul-Hassan Tawbi, Dirk Schadendorf, University of Zurich, and Schadendorf, Dirk
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Oncology ,Trametinib ,Cancer Research ,medicine.medical_specialty ,business.industry ,MEK inhibitor ,Melanoma ,Medizin ,10177 Dermatology Clinic ,610 Medicine & health ,Dabrafenib ,medicine.disease ,Clinical trial ,Internal medicine ,Medicine ,2730 Oncology ,1306 Cancer Research ,Anaplastic thyroid cancer ,business ,Lung cancer ,Adverse effect ,medicine.drug - Abstract
Background: Dabrafenib plus trametinib has demonstrated clinical benefit across multiple BRAF-mutant tumours, leading to approval for resected stage III and metastatic melanoma, non-small-cell lung cancer (NSCLC) and anaplastic thyroid cancer. Pyrexia is a common adverse event in patients treated with dabrafenib plus trametinib. Here, we characterise the incidence, patterns and management of pyrexia in patients receiving dabrafenib plus trametinib in clinical trials. Methods: Patients (N = 1076) included in the analysis received dabrafenib plus trametinib in the following clinical trials: phase II registration trial in advanced NSCLC (N = 82), phase III COMBI-AD study in resectable stage III melanoma (N = 435) and phase III COMBI-d and COMBI-v studies in unresectable or metastatic melanoma (N = 209 and N = 350, respectively). Results: Among the 1076 patients enrolled in the clinical trials, 61.3% developed pyrexia, 5.7% developed grade 3/4 pyrexia and 15.6% developed a protocol-defined serious pyrexia event. Among the 660 patients with pyrexia, 33.0% had 1 occurrence, 19.8% had 2 occurrences and 47.1% had ≥3 occurrences. The incidence of pyrexia was highest early in treatment and decreased with time on treatment. Temporary dose interruption of dabrafenib or trametinib was the most common and effective management strategy. Conclusions: Pyrexia is the most common adverse event associated with dabrafenib plus trametinib but is manageable with dose interruption. Trial registration: ClinicalTrials.gov (Phase II NSCLC, NCT01336634; COMBI-AD, NCT01682083; COMBI-d, NCT01584648; COMBI-v, NCT01597908). Keywords: Adverse event; BRAF V600–mutant melanoma; BRAF inhibitor; MEK inhibitor; Pyrexia.
- Published
- 2021
13. A phase 3 randomized study (HOMER) of ofatumumab vs rituximab in iNHL relapsed after rituximab-containing therapy
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Noriko Fukuhara, David G. Maloney, Hiya Banerjee, Miguel Izquierdo, Janet Lasher, Jaclyn Davis, Michinori Ogura, and Kensei Tobinai
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Oncology ,medicine.medical_specialty ,Lymphoma, B-Cell ,Clinical Trials and Observations ,medicine.medical_treatment ,Follicular lymphoma ,Antibodies, Monoclonal, Humanized ,Ofatumumab ,law.invention ,chemistry.chemical_compound ,Randomized controlled trial ,immune system diseases ,law ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Chemotherapy ,business.industry ,Hazard ratio ,Hematology ,medicine.disease ,Regimen ,chemistry ,Rituximab ,Neoplasm Recurrence, Local ,business ,medicine.drug - Abstract
Because of high relapse rates with rituximab combinations, there is an unmet need for new therapeutic agents for treatment of indolent B-cell non-Hodgkin lymphoma (iNHL) or follicular lymphoma (FL). In previous trials, ofatumumab in combination with chemotherapy showed good results in relapsed/refractory FL pretreated with rituximab. This phase 3 trial evaluated the efficacy and safety of single-agent ofatumumab vs single-agent rituximab in rituximab-sensitive relapsed FL that relapsed at least 6 months after completing the last prior treatment with single-agent rituximab or a rituximab-containing regimen. Patients were randomized 1:1 to receive either ofatumumab (1000 mg) or rituximab (375 mg/m2) every week for 4 weeks for the induction phase, followed by once every 2 months for 4 additional doses. The primary endpoint, progression-free survival (PFS) and secondary endpoints, overall response rate (ORR) and overall survival (OS), were evaluated. Overall, 438 patients were assigned to receive ofatumumab (n = 219) and rituximab (n = 219). Baseline characteristics were similar in both arms. The independent review committee assessed whether median PFS was shorter in the ofatumumab arm than in the rituximab arm (16.33 vs 21.29 months), with no significant difference (hazard ratio, 1.15; 95% confidence interval, 0.89-1.49; P = .29) and also showed a lower ORR (50%) compared with the rituximab arm (66%). At the time of analysis, data were not matured for OS results. The number of grade >3 adverse events was higher in the ofatumumab arm (37%) than the rituximab arm (28%). Ofatumumab showed no superiority over rituximab in patients with FL who had relapsed after a rituximab-containing therapy. This study was registered at www.clinicaltrials.gov as #NCT01200589.
- Published
- 2020
14. Author Correction: Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy
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Christopher P. Vellano, Michael G. White, Miles C. Andrews, Manoj Chelvanambi, Russell G. Witt, Joseph R. Daniele, Mark Titus, Jennifer L. McQuade, Fabio Conforti, Elizabeth M. Burton, Matthew J. Lastrapes, Gabriel Ologun, Alexandria P. Cogdill, Golnaz Morad, Peter Prieto, Alexander J. Lazar, Yanshuo Chu, Guangchun Han, M. A. Wadud Khan, Beth Helmink, Michael A. Davies, Rodabe N. Amaria, Jeffrey J. Kovacs, Scott E. Woodman, Sapna Patel, Patrick Hwu, Michael Peoples, Jeffrey E. Lee, Zachary A. Cooper, Haifeng Zhu, Guang Gao, Hiya Banerjee, Mike Lau, Jeffrey E. Gershenwald, Anthony Lucci, Emily Z. Keung, Merrick I. Ross, Laura Pala, Eleonora Pagan, Rossana Lazcano Segura, Qian Liu, Mikayla S. Borthwick, Eric Lau, Melinda S. Yates, Shannon N. Westin, Khalida Wani, Michael T. Tetzlaff, Lauren E. Haydu, Mikhila Mahendra, XiaoYan Ma, Christopher Logothetis, Zachary Kulstad, Sarah Johnson, Courtney W. Hudgens, Ningping Feng, Lorenzo Federico, Georgina V. Long, P. Andrew Futreal, Swathi Arur, Hussein A. Tawbi, Amy E. Moran, Linghua Wang, Timothy P. Heffernan, Joseph R. Marszalek, and Jennifer A. Wargo
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Multidisciplinary - Published
- 2023
15. Improved pyrexia-related outcomes associated with an adapted pyrexia adverse event management algorithm in patients treated with adjuvant dabrafenib plus trametinib: Primary results of COMBI-APlus
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Victoria Atkinson, Caroline Robert, Jean J. Grob, Helen Gogas, Caroline Dutriaux, Lev Demidov, Avinash Gupta, Alexander M. Menzies, Bettina Ryll, Flora Miranda, Hiya Banerjee, Mike Lau, and Michele Del Vecchio
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Proto-Oncogene Proteins B-raf ,Cancer Research ,Skin Neoplasms ,Fever ,Pyridones ,Imidazoles ,Pyrimidinones ,Oncology ,Adjuvants, Immunologic ,Antineoplastic Combined Chemotherapy Protocols ,Mutation ,Oximes ,Humans ,Neoplasm Recurrence, Local ,Melanoma ,Algorithms - Abstract
COMBI-AD demonstrated long-term benefit of adjuvant dabrafenib plus trametinib in patients with resected stage III BRAF V600E/K-mutant melanoma; however, 9% of patients permanently discontinued therapy due to pyrexia. COMBI-APlus evaluated whether an adapted pyrexia management algorithm reduces high-grade pyrexia and pyrexia-related adverse outcomes.COMBI-APlus is an open-label, phase IIIb trial evaluating an adapted pyrexia management algorithm in patients with high-risk resected stage III BRAF V600E/K-mutant melanoma treated with up to 12 months of adjuvant dabrafenib plus trametinib. Both drugs were interrupted for pyrexia (temperature ≥38°C) or the occurrence of pyrexia syndrome for suspected recurrent pyrexia. Treatment was restarted at the same dose once patients were symptom free for ≥24 h. The primary endpoint was the composite rate of grade 3/4 pyrexia, hospitalisation due to pyrexia, or permanent discontinuation due to pyrexia versus historical COMBI-AD control (20.0%; 95% confidence interval [CI], 16.3%-24.1%).At data cutoff (5 October 2020), COMBI-APlus met its primary endpoint of significant improvement in the composite rate of pyrexia (8.0% [95% CI, 5.9%-10.6%]), with rates of 3.8% for grade 3/4 pyrexia, 4.3% for hospitalisation due to pyrexia, and 2.4% for discontinuation due to pyrexia. Estimated 12-month relapse-free survival was 91.8% (95% CI, 89.0%-93.9%). The most common adverse events were consistent with those in COMBI-AD, and 14.7% of patients permanently discontinued treatment due to adverse events.The adapted pyrexia management algorithm appears to reduce the incidence of severe pyrexia outcomes, enables patients to manage pyrexia at home, and helps patients remain on treatment.NCT03551626.
- Published
- 2021
16. A Retrospective Analysis of Dabrafenib and/or Dabrafenib Plus Trametinib Combination in Patients with Metastatic Melanoma to Characterize Patients with Long-Term Benefit in the Individual Patient Program (DESCRIBE III)
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Michele Del Vecchio, Hiya Banerjee, Massimo Aglietta, Pier Francesco Ferrucci, Helen Gogas, Teddy Saliba, Roberta Depenni, Egbert de Jong, Pietro Quaglino, Francesca Consoli, Ana Arance, Skaiste Tulyte, Dimitrios Bafaloukos, Bart Neyns, Victoria Atkinson, Ivana Krajsová, Rossana Gueli, Paolo A. Ascierto, Clinical sciences, Medical Oncology, Laboratory of Molecular and Medical Oncology, and Laboratory of Molecullar and Cellular Therapy
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Oncology ,Cancer Research ,medicine.medical_specialty ,real-world ,BRAF V600 ,Chart review ,Dabrafenib ,Melanoma ,Real-world ,Trametinib ,Metastatic melanoma ,Combination therapy ,chart review ,dabrafenib ,melanoma ,trametinib ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,In patient ,030212 general & internal medicine ,RC254-282 ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,030220 oncology & carcinogenesis ,Observational study ,business ,medicine.drug - Abstract
The dabrafenib plus trametinib (dab + tram) combination has demonstrated durable long-term efficacy in patients with BRAF V600–mutant metastatic melanoma. However, real-world data characterizing patients with long-term benefit are limited. DESCRIBE III was a global, observational, retrospective, chart review study in patients with unresectable or metastatic melanoma treated with dab monotherapy and/or dab + tram combination therapy as part of the Named Patient Program or Individual Patient Program. Overall, 509 patients were enrolled. Patients were categorized into three groups based on their observed treatment duration: long-term (on therapy ≥12 months), intermediate (on therapy ≥6 months and <, 12 months), and short-term (on therapy <, 6 months) duration of benefit. More patients in the short-term duration of benefit group had baseline characteristics associated with poor prognosis compared with the other two groups. Median lactate dehydrogenase (LDH) levels (368 U/L) at baseline were also higher in the short-term duration of benefit group. No new safety signals were identified. DESCRIBE III identified baseline characteristics associated with long-term benefit of dab + tram. Lower LDH level and <, 3 metastatic sites at baseline were associated with a longer duration of benefit, confirming that the findings from COMBI-d and COMBI-v are relevant to patients treated in a real-world setting.
- Published
- 2021
17. Étude d’un algorithme adapté de gestion de la fièvre chez les patients traités par dabrafénib + tramétinib en adjuvant : premiers résultats de la cohorte française de COMBI-APlus
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Mike Lau, Jean-Jacques Grob, Caroline Robert, Laurent Mortier, Olivier Dereure, Hiya Banerjee, Thierry Lesimple, Philippe Saiag, Nicolas Meyer, S. Dalle, Caroline Dutriaux, Céleste Lebbé, Leila Benkanoun, F. Aubin, and Caroline Jacobzone
- Subjects
Ocean Engineering ,Safety, Risk, Reliability and Quality - Abstract
Introduction L’interet de dabrafenib trametinib (dab + tram) en adjuvant chez les patients (pts) ayant un melanome BRAF V600E/K mute de stade III reseque a ete demontre dans l’etude COMBI-AD. Dans COMBI-AD, les effets indesirables (EI) ont conduit a l’arret definitif de dab + tram chez 26 % des pts, principalement en raison de la fievre (9 %). L’objectif de COMBI-APlus ( NCT03551626 ) est d’evaluer un nouvel algorithme de gestion de la fievre pour reduire les grades 3/4 et ses consequences (arret du traitement, hospitalisation). Materiel et methodes COMBI-APlus est un essai ouvert de phase IIIb evaluant un algorithme de gestion de la fievre chez des pts ayant un melanome reseque de stade III BRAF V600E/K-mute traites en adjuvant par dab + tram pendant 12 mois. L’algorithme prevoit l’interruption de dab + tram des apparition d’une temperature ≥ 38 °C et la reprise a la meme dose des disparition des symptomes depuis 24 h. En cas de suspicion de fievre recurrente et en presence d’un syndrome febrile (frissons, raideurs, sueurs nocturnes, symptomes grippaux sans fievre) le traitement peut etre interrompu a la discretion de l’investigateur. Le critere d’evaluation principal est le taux composite de fievre (grades 3/4, hospitalisation ou arret definitif du traitement dus a la fievre) compare aux donnees historiques de COMBI-AD (20 % ; IC95 % : 16,3 %–24,1 %). Les criteres secondaires incluent la survie sans rechute (SSR) et l’innocuite. Resultats Cent soixante-seize pts ont ete inclus en France sur un total de 552 pts avec un suivi median de 18,14 mois. COMBI-APlus a atteint son critere principal d’amelioration significative du taux composite de fievre par rapport au temoin historique COMBI-AD. Il est de 7,4 % (IC95 % : 4,0 %–12,3 %) avec des taux de 4,0 % pour les grades 3/4, de 2,8 % pour les hospitalisations et de 3,4 % pour les arrets definitifs de traitement dus a la fievre. Le taux de SSR estime a 12 mois est de 90,9 % (IC95 % : 85,4 %–94,4 %). Les principaux EI ≥ 20 % sont : fievre (67,0 %), asthenie (48,9 %), cephalees (40,9 %), diarrhee (34,7 %), augmentation de la creatine phosphokinase sanguine (31,8 %), frissons (31,3 %), nausees (26,7 %), arthralgies (25,6 %), fatigue (22,2 %). L’ensemble des EI a conduit a l’arret definitif de dab + tram chez 14,2 % des pts versus 26 % dans COMBI-AD. Discussion Cette analyse suggere que ce nouvel algorithme simplifie de gestion de la fievre est efficace pour reduire le taux composite de fievre (grades 3/4, hospitalisation, arret de traitement) chez les pts recevant dab + tram en adjuvant. Les premiers resultats d’efficacite semblent correspondre a ceux observes dans COMBI-AD. Cet algorithme peut reduire le besoin d’hospitalisation ou de consultation liees a la fievre, ce qui est souhaitable dans le contexte actuel de pandemie du COVID-19. Ainsi plus de pts peuvent rester sous traitement et en tirer un benefice clinique.
- Published
- 2021
18. Abstract CT547: Neoadjuvant and adjuvant capmatinib in resectable non-small cell lung cancer with MET exon 14 skipping mutation or high MET amplification: GEOMETRY-N trial
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Jay M. Lee, Mark M. Awad, Teddy Saliba, Nydia Caro, Hiya Banerjee, and Karen Kelly
- Subjects
Cancer Research ,Oncology - Abstract
Background: Neoadjuvant therapy is the earliest opportunity to eliminate micrometastatic disease. Emerging data suggest that neoadjuvant therapy in non-small cell lung cancer (NSCLC) can elicit major pathological responses (MPRs) that translate into prolonged survival outcomes, serving as an early surrogate for efficacy. Adjuvant therapy can improve overall and disease-free survival (DFS) in patients with completely resected NSCLC. DFS observed with osimertinib in patients with early-stage EGFR-mutated tumors supports evaluation of other tyrosine kinase inhibitors (TKIs) in the neoadjuvant and adjuvant settings. In early-stage NSCLC, MET exon 14 skipping mutation (METex14) and de novo MET amplification (METamp) are estimated to occur in up to 2.8% and 1.7% of patients, respectively. Capmatinib, a selective MET TKI, is FDA approved for patients with metastatic METex14 NSCLC. It was studied in GEOMETRY mono-1 in patients with advanced/metastatic NSCLC with METex14 or METamp. In 2 treatment-naive METex14 cohorts, overall response rate (ORR) was 68% and 66%. In a treatment-naive high-level METamp cohort, ORR was 40%. Capmatinib had a tolerable safety profile; most adverse events were reversible with dose adjustments. Based on the response rates and safety profile observed in treatment-naive patients with advanced/metastatic MET-dysregulated NSCLC, GEOMETRY-N (NCT04926831), a Phase II, 2-cohort, 2-stage study, is evaluating the efficacy and safety of neoadjuvant and adjuvant capmatinib therapy in improving the MPR rate and outcomes in patients with METex14 or high-level METamp NSCLC. Methods: Adults with resectable, histologically confirmed NSCLC stage IB-IIIA, N2 and select IIIB (T3N2 or T4N2) with either METex14 (cohort A) or high-level METamp (gene copy number ≥10; cohort B) are eligible. METex14 must be determined by a Clinical Laboratory Improvement Amendments (CLIA)-certified lab. METamp must be determined by fluorescence in situ hybridization at a CLIA-certified lab or by FoundationOne CDx next-generation sequencing. Prior systemic anticancer therapy is prohibited. Patients will receive capmatinib 400 mg twice daily for 8 weeks before surgical resection, followed by 3 years of adjuvant capmatinib. In the 2-stage design, stage 1 will enroll 9 patients per cohort, with MPR evaluated in each cohort after 9 patients have completed neoadjuvant therapy; stage 2, enrolling 10 more patients in a cohort, will proceed only if ≥1 of 9 participants has an MPR. About 42 patients will be enrolled, with 19 evaluable patients per cohort. The primary endpoint is MPR rate (local assessment). Secondary endpoints are complete pathological response rate (central and local review), ORR (local assessment), DFS, and safety. Following treatment, there will be a 2-year survival follow-up. The expected first patient first visit is December 30, 2021. Citation Format: Jay M. Lee, Mark M. Awad, Teddy Saliba, Nydia Caro, Hiya Banerjee, Karen Kelly. Neoadjuvant and adjuvant capmatinib in resectable non-small cell lung cancer with MET exon 14 skipping mutation or high MET amplification: GEOMETRY-N trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT547.
- Published
- 2022
19. Neoadjuvant and adjuvant capmatinib in resectable non–small cell lung cancer with MET exon 14 skipping mutation or high MET amplification: GEOMETRY-N trial
- Author
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Jay M. Lee, Mark M. Awad, Teddy Rassem Saliba, Nydia Caro, Hiya Banerjee, and Karen Kelly
- Subjects
Cancer Research ,Oncology - Abstract
TPS8590 Background: Neoadjuvant therapy is the earliest opportunity to eliminate micrometastatic disease. Emerging data suggest that neoadjuvant therapy in non-small cell lung cancer (NSCLC) can elicit major pathological responses (MPRs) that translate into prolonged survival outcomes, serving as an early surrogate for efficacy. Adjuvant therapy can improve overall and disease-free survival (DFS) in patients with completely resected NSCLC. DFS observed with osimertinib in patients with early-stage EGFR-mutated tumors supports evaluation of other tyrosine kinase inhibitors (TKIs) in the neoadjuvant and adjuvant settings. In early-stage NSCLC, MET exon 14 skipping mutation ( METex14) and de novo MET amplification ( METamp) are estimated to occur in up to 2.8% and 1.7% of patients, respectively. Capmatinib, a selective MET TKI, is FDA approved for patients with metastatic METex14 NSCLC. It was studied in GEOMETRY mono-1 in patients with advanced/metastatic NSCLC with METex14 or METamp. In 2 treatment-naive METex14 cohorts, overall response rate (ORR) was 68% and 66%. In a treatment-naive high-level METamp cohort, ORR was 40%. Capmatinib had a tolerable safety profile; most adverse events were reversible with dose adjustments. Based on the ORRs and safety profile observed in treatment-naive patients with advanced/metastatic MET-dysregulated NSCLC, GEOMETRY-N (NCT04926831), a Phase II, 2-cohort, 2-stage study, is evaluating the efficacy and safety of neoadjuvant and adjuvant capmatinib therapy in improving the MPR rate and outcomes in patients with METex14 or high-level METamp NSCLC. Methods: Adults with resectable, histologically confirmed NSCLC stage IB-IIIA, N2 and select IIIB (T3N2 or T4N2) with either METex14 (cohort A) or high-level METamp (gene copy number ≥10; cohort B) are eligible. METex14 must be determined by a Clinical Laboratory Improvement Amendments (CLIA)-certified lab. METamp must be determined by fluorescence in situ hybridization at a CLIA-certified lab or by FoundationOne CDx next-generation sequencing. Prior systemic anticancer therapy is prohibited. Patients will receive capmatinib 400 mg twice daily for 8 weeks before surgical resection, followed by 3 years of adjuvant capmatinib. In the 2-stage design, stage 1 will enroll 9 patients per cohort, with MPR evaluated in each cohort after 9 patients have completed neoadjuvant therapy; stage 2, enrolling 10 more patients in a cohort, will proceed only if ≥1 of 9 participants has an MPR. About 42 patients will be enrolled, with 19 evaluable patients per cohort. Primary endpoint is MPR rate (local assessment). Secondary endpoints are complete pathological response rate (central and local review), ORR (local assessment), DFS, and safety. Following treatment, there will be a 2-year survival follow-up. Enrollment has started; expected first patient first visit: March 31, 2022. Clinical trial information: NCT04926831.
- Published
- 2022
20. Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy
- Author
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Michael White, Christopher P. Vellano, Miles Cameron Andrews, Russell G. Witt, Manoj Chelvanambi, Jennifer Leigh McQuade, Elizabeth M. Burton, Yanshuo Chu, Matthew J Lastrapes, Mike R. Lau, Hiya Banerjee, Alexander J. Lazar, Michael A. Davies, Scott Eric Woodman, Linghua Wang, Amy E. Moran, Georgina V. Long, Timothy Heffernan, Joe R. Marszalek, and Jennifer Ann Wargo
- Subjects
Cancer Research ,Oncology - Abstract
9523 Background: Treatment with BRAF+/-MEK inhibition (BRAF+/-MEKi) has revolutionized treatment in melanoma and other cancers, but resistance is common and innovative treatment strategies are needed. Sexual dimorphism in response to BRAF+/-MEKi have been noted, but mechanisms behind this are poorly understood and hormonal modulation has not been well-studied in this setting. Methods: We examined outcomes by sex in five clinical cohorts of patients (pts) (total n = 792, 362 female, 430 male) with BRAF-mutated melanoma who were treated with BRAF/MEKi in either the neoadjuvant or metastatic setting. Rates of major pathologic response (MPR), clinical benefit (CB), progression free survival (PFS) relapse-free survival (RFS) and overall survival (OS) were assessed. Translational research studies were performed on available pre- and on-treatment tumor samples (n = 27 pts) including RNA sequencing and profiling androgen receptor (AR) expression. Parallel studies were performed in preclinical models to assess the effect of sex and AR modulation on response to BRAF+/-MEKi. Results: In this study, improved rates of MPR, CB, PFS and OS were observed in female vs male pts. Specifically, female patients treated with neoadjuvant BRAF+MEKi showed significantly higher rates of MPR (66% v. 14%, p = 0.001), and improved RFS (64% versus 32% at 2 years, p = 0.021) vs male pts in the neoadjuvant setting (n = 51). These findings were not observed in a 2nd smaller trial of pts (n = 35), but were validated in a cohort of pts with unresectable metastatic melanoma treated with BRAF+MEKi (n = 69), with significantly higher rates of CB (80% v. 68%, p = 0.022) and PFS (12 v. 7 months, p = 0.003) in female vs male pts. Data from several published trials was analyzed (COMBI-D and METRIC trials), demonstrating improved PFS/OS at 2 years in female vs male pts treated with combined BRAF/MEKi (n = 211; p = 0.03 and, p = 0.04) and in female vs male pts treated with MEKi monotherapy (n = 206; p = 0.04 and p = 0.002), but not in female vs male pts treated with BRAFi monotherapy (n = 211; p = 0.21 and 0.095). Significantly higher expression AR expression was observed in available on- vs pre-treatment samples from male pts (p = 0.01), suggesting that treatment with BRAF/MEKi may induce AR expression in tumors. Findings were recapitulated in several preclinical models, and treatment with pharmacologic inhibitors of AR signaling (enzalutamide) in combination with BRAF/MEKi was associated with significantly enhanced anti-tumor activity in both male and female mice (p = 0.003 and p < 0.0001). Conversely, systemic treatment with testosterone was associated with significantly impaired tumor control in male and female mice (p = 0.021 and < 0.001). Conclusions: These data suggest that AR blockade may promote BRAF/MEKi response in melanoma, warranting further investigation in clinical trials. The impact of AR signaling, and modulation should be studied in MAPK-targeted therapy across other cancer types.
- Published
- 2022
21. Adjuvant dabrafenib plus trametinib (D + T) versus placebo in patients with resected stage III BRAFV600-mutant melanoma: Updated 5-year distant metastases-free survival (DMFS) analysis of COMBI-AD
- Author
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Dirk Schadendorf, Axel Hauschild, Mario Mandalà, John M. Kirkwood, Caroline Robert, Jean-Jacques Grob, Paul D. Nathan, Michael A. Davies, Hiya Banerjee, Rohan Shah, Mike R. Lau, Reinhard Dummer, and Georgina V. Long
- Subjects
Cancer Research ,Oncology - Abstract
9563 Background: DMFS is an important endpoint for patients with stage III cutaneous melanoma, as delaying or preventing systemic disease is associated with improved clinical and patient-reported outcomes. Prior results from the phase 3 COMBI-AD trial (NCT01682083) showed 5-year DMFS rates of 65% with adjuvant D + T vs 54% with placebo (PBO; hazard ratio [HR] = 0.55; 95% CI: 0.44-0.70). An analysis of DMFS by AJCC-7 stages IIIA-C suggested a similar benefit of D + T vs PBO regardless of stage (Dummer R et al. N Engl J Med. 2020). Here, we report 5-year DMFS rates by AJCC-8 stages IIIA-D, other prognostic subgroups, and results of a regression tree analysis with DMFS. Methods: Patients with resected AJCC-7 stage III BRAFV600E/K-mutant melanoma were randomized to either D (150 mg twice daily) + T (2 mg once daily) or 2 matched PBOs for 12 months. Primary endpoint was relapse-free survival (RFS); DMFS was a secondary endpoint. Kaplan-Meier survival analyses were performed to assess the long-term benefits for DMFS rates with D + T vs PBO. The regression tree analysis (data cutoff: 5 years) for all patients (N = 870) evaluated potential prognostic/predictive factors of long-term DMFS including baseline age, sex, region, BRAF mutation type, body mass index, lactate dehydrogenase levels, ECOG, T and N categories, histology, primary tumor ulceration, treatment type, number of lymph nodes with metastases, tumor mutational burden, and interferon-gamma gene expression signature (IFN-γ GES). Results: At 5 years, DMFS rates were higher for patients with AJCC-8 stages IIIB-D disease receiving adjuvant D + T vs PBO (table). Five-year DMFS rates also favored D + T vs PBO in subgroups of patients with microscopic or macroscopic lymph node involvement (table) and those with or without primary tumor ulceration and/or in-transit metastases. A regression tree revealed T and N stage, treatment type, and IFN-γ GES as important variables defining 5-year DMFS subgroups. Conclusions: In this retrospective analysis, adjuvant D + T provided long-term DMFS benefit vs PBO in stage IIIB-D patients with resected BRAFV600E/K-mutant melanoma. Key clinical and patient factors impacting DMFS were similar to prior RFS findings (ESMO 2021; Robert C et al. Ann Oncol. 2021) and included T and N stage, treatment type, and IFN-γ GES. These results further validate the robust long-term clinical benefit of adjuvant D + T for patients with melanoma. Clinical trial information: NCT01682083. [Table: see text]
- Published
- 2022
22. 1075P Regression tree analysis to identify factors associated with relapse-free survival (RFS) in patients with resected stage III BRAF V600E/K–mutant melanoma
- Author
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Kelly Biette, Michael A. Davies, J.-J. Grob, Paul Nathan, Mario Mandalà, Hiya Banerjee, John M. Kirkwood, Dirk Schadendorf, Mike Lau, Aislyn Boran, Caroline Robert, Axel Hauschild, Reinhard Dummer, B.G. Sahoo, and Georgina V. Long
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Melanoma ,Regression tree analysis ,Mutant ,Hematology ,medicine.disease ,Relapse free survival ,BRAF V600E ,Internal medicine ,medicine ,In patient ,Stage (cooking) ,business - Published
- 2021
23. A 5-year follow-up to evaluate the efficacy and safety of ofatumumab added to fludarabine and cyclophosphamide in patients with relapsed chronic lymphocytic leukemia: final analysis of the COMPLEMENT 2 trial
- Author
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Elena Litvinskaya, Janusz Kloczko, Tadeusz Robak, Ewa Lech-Marańda, Justyna Rybka, Grygoriy Rekhtman, Sebastian Grosicki, Wojciech Homenda, Javier Loscertales, Tommaso Stefanelli, Iryna Kriachok, Ghislaine Vincent, Kanakasetty Govind Babu, Jerzy Z. Blonski, and Hiya Banerjee
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Cyclophosphamide ,medicine.drug_class ,Chronic lymphocytic leukemia ,Monoclonal antibody ,Ofatumumab ,Antibodies, Monoclonal, Humanized ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,In patient ,business.industry ,Hematology ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Complement (complexity) ,Fludarabine ,Treatment Outcome ,chemistry ,030220 oncology & carcinogenesis ,Rituximab ,sense organs ,business ,Vidarabine ,030215 immunology ,medicine.drug ,Follow-Up Studies - Abstract
Anti-CD20 monoclonal antibodies (mAbs) in combination with chemotherapies have changed the treatment landscape for chronic lymphocytic leukemia (CLL) [1]. Rituximab added to fludarabine with cyclop...
- Published
- 2020
24. Pazopanib Exposure Relationship with Clinical Efficacy and Safety in the Adjuvant Treatment of Advanced Renal Cell Carcinoma
- Author
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Hiya Banerjee, Naomi B. Haas, Christian Doehn, Robert J. Motzer, Paul Russo, Frede Donskov, Mohamed Elmeliegy, Guillaume Baneyx, Cora N. Sternberg, and Paola Aimone
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Indazoles ,Population ,Angiogenesis Inhibitors ,Antineoplastic Agents ,Gastroenterology ,law.invention ,Pazopanib ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Renal cell carcinoma ,Internal medicine ,Carcinoma ,medicine ,Humans ,030212 general & internal medicine ,Neoplasm Metastasis ,education ,Adverse effect ,Carcinoma, Renal Cell ,Protein Kinase Inhibitors ,Neoplasm Staging ,Sulfonamides ,education.field_of_study ,business.industry ,medicine.disease ,Kidney Neoplasms ,Confidence interval ,Discontinuation ,Pyrimidines ,Treatment Outcome ,Oncology ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Female ,business ,medicine.drug - Abstract
Purpose: PROTECT, a phase III, randomized, placebo-controlled study, evaluated pazopanib efficacy and safety in the adjuvant renal cell carcinoma setting. The relationship between pazopanib exposure (Ctrough) and efficacy and safety was evaluated. Patients and Methods: Evaluable steady-state blood trough concentrations were collected from 311 patients at week 3 or 5 (early Ctrough) and 250 patients at week 16 or 20 (late Ctrough). Pazopanib pharmacokinetic (PK) data were analyzed via a population model approach. Relationship between Ctrough or dose intensity and disease-free survival (DFS) was explored via Kaplan–Meier and multivariate analysis. Adverse events (AE) and AE-related treatment discontinuation proportions were summarized by Ctrough quartiles. Results: Most (>90%) patients with early or late Ctrough data started on 600 mg. Mean early and late Ctrough overlapped across dose levels. Patients with higher early Ctrough quartiles achieved longer DFS (adjusted HR, 0.58; 95% confidence interval, 0.42–0.82; P = 0.002). Patients achieving early or late Ctrough >20.5 μg/mL had significantly longer DFS: not estimable (NE) versus 29.5 months, P = 0.006, and NE versus 29.9 months, P = 0.008, respectively. Dose intensity up to week 8 did not correlate with DFS, consistent with population PK model–based simulations showing overlapping pazopanib exposure with 600 and 800 mg doses. The proportion of AE-related treatment discontinuation and grade 3/4 AEs, with the exception of hypertension, was not correlated to Ctrough. Conclusions: In the adjuvant setting, higher pazopanib Ctrough was associated with improved DFS and did not increase treatment discontinuations or grade 3/4 AEs, with the exception of hypertension. Clin Cancer Res; 24(13); 3005–13. ©2018 AACR. See related commentary by Rini, p. 2979
- Published
- 2018
25. Abstract LBA046: Neoadjuvant and Adjuvant Capmatinib in Resectable Non-Small Cell Lung Cancer With MET Exon 14 Skipping Mutation or High MET Amplification: GEOMETRY-N Trial
- Author
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Karen Kelly, Mark M. Awad, Teddy Saliba, Nydia Caro, Beth Inserra, Hiya Banerjee, and Jay M. Lee
- Subjects
Cancer Research ,Oncology - Abstract
Background: Neoadjuvant therapy is the earliest opportunity to eliminate micrometastatic disease. Emerging data suggest that neoadjuvant therapy in non-small cell lung cancer (NSCLC) can elicit major pathological responses (MPRs) that translate into prolonged survival outcomes, serving as an early surrogate for efficacy. Adjuvant therapy is well known to improve overall and disease-free survival (DFS) in patients with completely resected NSCLC. DFS observed with osimertinib in patients with early-stage EGFR-mutated tumors supports evaluation of other tyrosine kinase inhibitors (TKIs) in the neoadjuvant and adjuvant settings. In early-stage NSCLC, MET exon 14 skipping mutation (METex14) and de novo MET amplification (METamp) are estimated to occur in up to 2.8% and 1.7% of patients, respectively. Capmatinib, a selective MET TKI, is FDA approved for patients with metastatic METex14 NSCLC. It was studied in GEOMETRY mono-1 in patients with advanced/metastatic NSCLC with either METex14 or METamp. In two treatment-naive METex14 cohorts, overall response rate (ORR) was 68% and 66%. In a treatment-naive high-level METamp cohort, ORR was 40%. Capmatinib had a tolerable safety profile; most adverse events were reversible with dose adjustments. Based on the response rates and the safety profile observed in GEOMETRY mono-1 in treatment-naive patients with advanced/metastatic MET-dysregulated NSCLC, GEOMETRY-N (NCT04926831) a Phase II, two-cohort, two-stage study is evaluating the efficacy and safety of neoadjuvant and adjuvant capmatinib therapy in improving the MPR rate and outcomes beyond those achieved with surgery, chemotherapy, and radiation in patients with METex14 or high-level METamp NSCLC. Methods: Adult patients with resectable, histologically confirmed NSCLC stage IB-IIIA, N2 and select IIIB (T3N2 or T4N2) with either METex14 irrespective of MET gene copy number (GCN) (cohort A) or high-level METamp with GCN ≥10 (cohort B) are eligible. METex14 must be determined by a Clinical Laboratory Improvement Amendments (CLIA)-certified lab. METamp must be determined by fluorescent in situ hybridization at a CLIA-certified lab or by FoundationOne CDx next-generation sequencing. Prior systemic anticancer therapy is prohibited. Patients will receive capmatinib 400 mg twice daily for 8 weeks prior to surgical resection, followed by 3 years of adjuvant capmatinib. In the two-stage design, stage 1 will enroll 9 patients in each cohort, with MPR evaluated in each cohort after 9 patients have completed neoadjuvant therapy; stage 2, enrolling 10 more patients in a cohort, will proceed only if ≥1 of 9 participants has an MPR. About 42 patients will be enrolled, with 19 evaluable patients per cohort. The primary endpoint is MPR rate based on local investigator assessment. Secondary endpoints are complete pathological response rate (central and local investigator review), ORR (local investigator assessment), DFS, and safety. Following treatment, there will be a 2-year survival follow-up. The expected first patient first visit is September 30, 2021. Citation Format: Karen Kelly, Mark M. Awad, Teddy Saliba, Nydia Caro, Beth Inserra, Hiya Banerjee, Jay M. Lee. Neoadjuvant and Adjuvant Capmatinib in Resectable Non-Small Cell Lung Cancer With MET Exon 14 Skipping Mutation or High MET Amplification: GEOMETRY-N Trial [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA046.
- Published
- 2021
26. Improved pyrexia-related outcomes associated with an adapted pyrexia adverse event (AE) management algorithm in patients (pts) treated with adjuvant dabrafenib + trametinib (dab + tram): Primary results of COMBI-APlus
- Author
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Mike Lau, Caroline Dutriaux, J.-J. Grob, Hiya Banerjee, A. Gupta, Lev V. Demidov, B. Ryll, C. Robert, A.M. Menzies, M. Del Vecchio, Victoria Atkinson, Flora Miranda, and Helen Gogas
- Subjects
Oncology ,Trametinib ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Melanoma ,COVID-19 ,Dabrafenib ,bacterial infections and mycoses ,medicine.disease ,complex mixtures ,Management algorithm ,Discontinuation ,Coronavirus ,Internal medicine ,parasitic diseases ,medicine ,Stage (cooking) ,business ,Adverse effect ,Adjuvant ,medicine.drug - Abstract
9525 Background: The long-term benefit of adjuvant dab + tram in pts with resected stage III BRAF V600E/K–mutant melanoma was demonstrated in COMBI-AD where AEs led to permanent discontinuation of dab + tram in 26% of pts, most often due to pyrexia (9%). The COMBI-APlus trial (NCT03551626) is designed to evaluate whether an adapted pyrexia management algorithm could reduce high-grade pyrexia and other pyrexia-related adverse outcomes, such as treatment cessation and hospitalization. Methods: COMBI-APlus is an open-label, Phase IIIb trial evaluating an adapted pyrexia management algorithm in pts with high-risk resected stage III BRAF V600E/K–mutant melanoma treated with 12 mo of adjuvant dab + tram. In the adapted algorithm, both dab and tram were interrupted promptly at the onset of pyrexia (temperature ≥ 38°C). In the event of suspected recurrent pyrexia, treatment may be interrupted in the presence of pyrexia syndrome (ie, chills, rigors, night sweats, or influenza-like symptoms without temperature ≥ 38°C) at investigator discretion. Treatment with dab + tram was restarted at the same dose level once pts were symptom free for ≥ 24 hours. The primary endpoint is the composite rate of grade 3/4 pyrexia, hospitalization due to pyrexia, or permanent discontinuation due to pyrexia vs a historical control from COMBI-AD (20%; 95% CI, 16.3%-24.1%). Secondary endpoints include relapse-free survival (RFS) and safety. Results: A total of 552 pts were enrolled. At the data cutoff (5 Oct 2020), all pts had completed 12 mo of treatment; median duration of follow-up was 18.4 mo. COMBI-APlus met its primary endpoint of significant improvement in composite rate of pyrexia. The composite rate was 8.0% (95% CI, 5.9%-10.6%), with rates of 3.8% for grade 3/4 pyrexia, 4.3% for hospitalization due to pyrexia, and 2.4% for discontinuation due to pyrexia. The estimated 12-mo RFS rate was 91.8% (95% CI, 89.0%-93.9%). The most common AEs (≥ 20%) were pyrexia (67.8%), headache (31.7%), blood creatine phosphokinase increase (27.9%), diarrhoea (27.0%), chills (26.4%), fatigue (25.7%), asthenia (23.6%), nausea (23.4%), rash (21.4%), and arthralgia (21.0%). AEs of any type led to permanent dab + tram discontinuation in 14.7% of pts. Conclusions: This primary analysis suggests the new adapted pyrexia management algorithm is effective in reducing grade 3/4 pyrexia, pyrexia-related hospitalization, and treatment discontinuation in pts receiving adjuvant dab + tram. The early efficacy appears consistent with that observed in COMBI-AD. The growing experience of oncologists in managing pyrexia with this simple algorithm may reduce the need for hospitalization or visits to a healthcare provider, which is highly desirable during the current COVID-19 pandemic. Thus, more pts can remain on treatment and derive benefit. Clinical trial information: NCT03551626.
- Published
- 2021
27. 1100P Restricted mean survival time (RMST) and cure-rate modeling in estimating survival benefit with adjuvant dabrafenib (D) plus trametinib (T) treatment in melanoma
- Author
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John M. Kirkwood, Mario Santinami, Tomas Haas, C. Robert, J.M.G. Larkin, Monique Tan, C. Dutriaux, Dirk Schadendorf, Laurent Mortier, Georgina V. Long, Jacob Schachter, Mike Lau, Axel Hauschild, Hiya Banerjee, Andrew Haydon, Reinhard Dummer, Victoria Atkinson, Mario Mandalà, Marta Nyakas, and V. Chiarion Sileni
- Subjects
Trametinib ,Oncology ,medicine.medical_specialty ,Cure rate ,business.industry ,medicine.medical_treatment ,Melanoma ,Dabrafenib ,Hematology ,medicine.disease ,Survival benefit ,Mean Survival Time ,Internal medicine ,RMST ,medicine ,business ,Adjuvant ,medicine.drug - Published
- 2020
28. Ofatumumab maintenance prolongs progression-free survival in relapsed chronic lymphocytic leukemia : final analysis of the PROLONG study
- Author
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Marinus H. J. van Oers, Sebastian Grosicki, Lukas Smolej, Tommaso Stefanelli, Mark-David Levin, Jaclyn Davis, Fritz Offner, Mario Petrini, Petra Hoever, Hiya Banerjee, Christian H. Geisler, Clinical Haematology, and CCA - Cancer Treatment and Quality of Life
- Subjects
Male ,Lymphoma ,Cancer therapy ,MULTICENTER ,Gastroenterology ,THERAPY ,chemistry.chemical_compound ,DOUBLE-BLIND ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Recurrence ,Medicine and Health Sciences ,Medicine ,VENETOCLAX ,030212 general & internal medicine ,IBRUTINIB ,Aged, 80 and over ,RITUXIMAB MAINTENANCE ,Hazard ratio ,Hematology ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,OPEN-LABEL ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Ibrutinib ,Retreatment ,Female ,Adult ,medicine.medical_specialty ,Neutropenia ,Antibodies, Monoclonal, Humanized ,Ofatumumab ,lcsh:RC254-282 ,Article ,Maintenance Chemotherapy ,03 medical and health sciences ,Chemoimmunotherapy ,Internal medicine ,Humans ,Progression-free survival ,CHEMOIMMUNOTHERAPY ,Aged ,business.industry ,Venetoclax ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,LENALIDOMIDE MAINTENANCE ,chemistry ,business ,Febrile neutropenia ,RESISTANCE - Abstract
We report the final analysis of the PROLONG study on ofatumumab maintenance in relapsed chronic lymphocytic leukemia (CLL). In all, 480 patients with CLL in complete or partial remission after second- or third-line treatment were randomized 1:1 to ofatumumab (300 mg first week, followed by 1000 mg every 8 weeks for up to 2 years) or observation. Median follow-up duration was 40.9 months. Median progression-free survival was 34.2 and 16.9 months for ofatumumab and observation arms, respectively, (hazard ratio, 0.55 [95% confidence interval, 0.43–0.70]; P P = 0.0044). Overall survival was similar in both arms; median was not reached (0.99 [0.72–1.37]). Grade ≥ 3 adverse events occurred in 62% and 51% of patients in ofatumumab and observation arms, respectively, the most common being neutropenia (23% and 10%), pneumonia (13% and 12%) and febrile neutropenia (6% and 4%). Up to 60 days after the last treatment, four deaths were reported in the ofatumumab arm versus six in the observation arm, none considered related to ofatumumab. Ofatumumab maintenance significantly prolonged progression-free survival in patients with relapsed CLL and was well tolerated.
- Published
- 2019
29. Restricted Mean Survival Time and Cure-Rate Modeling in Estimating Relapse-Free Survival Benefit With Adjuvant Dabrafenib + Trametinib Treatment in Melanoma
- Author
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John M. Kirkwood, Monique Tan, Caroline Dutriaux, James E. Larkin, Dirk Schadendorf, Vanna Chiarion Sileni, Reinhard Dummer, Laurent Mortier, Georgina V. Long, Andrew Haydon, Mario Santinami, Mike Lau, Jacob Schachter, Caroline Robert, Axel Hauschild, Victoria Atkinson, Tomas Haas, Hiya Banerjee, Mario Mandalà, and Marta Nyakas
- Subjects
Oncology ,Trametinib ,medicine.medical_specialty ,business.industry ,MEK inhibitor ,Melanoma ,medicine.medical_treatment ,Dabrafenib ,medicine.disease ,Relapse free survival ,Mean Survival Time ,Internal medicine ,Adjuvant therapy ,Medicine ,business ,Adjuvant ,medicine.drug - Abstract
not available.
- Published
- 2021
30. Long-Term Evaluation of Efficacy and Safety of Ofatumumab Added to Fludarabine & Cyclophosphamide in Subjects with Relapsed Chronic Lymphocytic Leukemia: Final Analysis of Complement 2 Trial
- Author
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Justyna Rybka, Wojciech Homenda, Elena Litvinskaya, Jerzy Z. Blonski, Ewa Lech-Marańda, Tommaso Stefanelli, Sebastian Grosicki, Ghislaine Vincent, Tadeusz Robak, Janusz Kloczko, K Govind Babu, Hiya Banerjee, Grygoriy Rekhtman, Javier Loscertales, and Irina Kryachok
- Subjects
medicine.medical_specialty ,Cyclophosphamide ,Surrogate endpoint ,business.industry ,Immunology ,Hazard ratio ,Cell Biology ,Hematology ,Neutropenia ,medicine.disease ,Ofatumumab ,Interim analysis ,Biochemistry ,Gastroenterology ,Fludarabine ,chemistry.chemical_compound ,chemistry ,Internal medicine ,medicine ,business ,Febrile neutropenia ,medicine.drug - Abstract
Introduction: COMPLEMENT 2 is a phase III, randomized, open-label study, which compared the efficacy of ofatumumab (OFA) in combination with fludarabine and cyclophosphamide (FC) vs FC therapy alone in patients (pts) with relapsed chronic lymphocytic leukemia (CLL). In a previous interim analysis (2015) performed based on 194 progression-free survival (PFS) events, OFA+FC showed significant improvement of PFS and was well tolerated compared to FC in pts with relapsed CLL. Here, we report the 5-year follow-up of overall survival (OS) and safety profile of the drugs evaluated in this study. Methods: Based on stratification factors (number of prior CLL therapies and Binet stage), pts with relapsed CLL were randomized 1:1 to Arm A (OFA+FC) and Arm B (FC alone). Arm A received OFA intravenously (IV) (300 mg on day 1, cycle [c] 1; 1000 mg on day 8, c1; and 1000 mg on day 1, c2-6) in addition to FC (F [IV]: 25 mg/m2 and C [IV]: 250 mg/m2 on days 1-3, c1-6). Arm B received FC only. Pts who had achieved a complete response or partial response following at least 1 prior CLL therapy, but whose disease had progressed after >6 months (mo) were included in the present study. The primary endpoint was PFS. Key secondary endpoints were OS, time to next treatment (TTNT), and safety. During the primary analysis for PFS, all the type 1 error (1-sided alpha 0.025) was spent, resulting in no alpha remaining for inferential interpretation of the final analysis for OS. The final analysis results will be used for descriptive and supportive purposes only. Results: A total of 365 pts were randomly assigned to receive OFA+FC (n=183) or FC (n=182) in the final analysis. Overall, 119 (65%) and 102 (56%) pts completed the scheduled OFA+FC and FC treatments, respectively. Adverse events (AEs) were the main reason for treatment discontinuation in both treatment arms (50 [27%] pts in the OFA+FC arm and 52 [29%] in the FC arm). A total of 332 (91%) pts entered the follow-up phase, 172 (94%) from the OFA+FC arm and 160 (88%) from the FC arm. The follow-up phase for the OFA+FC and FC arms was approximately 41 mo and 23 mo, respectively. Baseline characteristics were similar in both arms. Median PFS was not assessed for the final analysis because the final results for the primary endpoint of PFS were reported as part of the primary analysis. PFS was 28.9 mo for OFA+FC and 18.8 mo for FC (hazard ratio [HR]=0.67, 95% confidence interval [CI]: 0.51, 0.88; p=0.0032). The final OS analysis was performed based on 82 events in the OFA+FC arm and 83 events in the FC arm. Median OS was 62.6 mo (95% CI: 44.58, NA) and 46.2 mo (95% CI: 37.72, 56.57) for the OFA+FC and FC arms, respectively (HR=0.80, 95% CI: 0.59, 1.09; p=0.143) (Figure 1). Median TTNT in the OFA+FC and FC arms was 53 mo and 40.1 mo, respectively (HR=0.77, 95% CI: 0.55, 1.08; p=0.114). As per the primary analysis, the overall response rate (95% CI) by independent review committee assessment (IRC) was 84% (77%, 89%) for OFA+FC and 68% (60%, 74%) for FC (p=0.0003). Other secondary endpoints (in mo) for OFA+FC vs FC were IRC-assessed median time to response (1 vs 1; HR=1.08, 95% CI: 0.85, 1.37; p=0.45), median duration of response (29.6 vs 24.9; HR=0.77, 95% CI: 0.56, 1.05; p=0.09), and median time to progression (42.1 vs 26.8; HR=0.63, 95% CI: 0.45, 0.87; p=0.004). All AEs and AEs of grade 3, 4, and 5 by preferred term (≥10%) are presented in Table 1. Serious drug-related AEs (≥2%) in the OFA+FC arm were pneumonia (8%), neutropenia and febrile neutropenia (7% each), and thrombocytopenia, pancytopenia, and pyrexia (2% each). Myelodysplastic syndrome was the most frequently reported secondary malignancy observed in ≥1% of pts (OFA+FC, 3 [2%]; FC, 2 [1%]). A total of 82 (45%) and 83 (47%) pts died during the study in the OFA+FC and FC arms, respectively; 2 (1%) and 6 (3%) died up to 60 days after the end of treatment, and 74 (41%) and 69 (39%) after >60 days. Three (2%) on-treatment deaths were reported in the OFA+FC arm and 4 (2%) in the FC arm. Conclusion: This final analysis confirmed the results of the primary analysis that addition of OFA to FC resulted in improvement of OS and TTNT by approximately 16 mo and 13 mo, respectively, compared to FC alone. Of note, the trend in the OS improvement seems to be maintained in the present long-term follow-up at 5 years. No new safety concerns have emerged in the long-term follow-up after treatment with OFA+FC, and the treatment was well tolerated. Disclosures Grosicki: Affimed: Research Funding. Lech-Maranda:Roche: Consultancy; Jansen-Cilag: Consultancy; Novartis: Consultancy; BMS: Consultancy; Amgen: Consultancy. Loscertales:Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Homenda:Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Rigel: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Acerta: Consultancy, Honoraria. Blonski:Novartis: Consultancy. Stefanelli:Novartis: Employment, Equity Ownership. Vincent:Novartis: Employment. Banerjee:Novartis: Employment. Robak:AbbVie, Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy.
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- 2018
31. Methods of finding the initial values of parameters in the maximum likelihood estimating equations for a logistic regression model and comparison of their final solutions using different criterion functions
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Hiya Banerjee and Subir Ghosh
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Statistics and Probability ,Iterative method ,Search algorithm ,Statistics ,Applied mathematics ,Value (computer science) ,CPU time ,Estimating equations ,Expression (computer science) ,Bayesian inference ,Jackknife resampling ,Mathematics - Abstract
We present two methods of finding the initial values of parameters of the maximum likelihood estimating equations (MLEE) for a logistic regression model using two criterion functions. We then use the initial values and the corresponding criterion functions to obtain the final solutions of MLEE. Most experiments include more than two doses for determining a lethal dose like E D 50 . With more than two doses, we do not have an exact analytical expression for the solution of estimating equations. However, for two doses, we do have an exact analytic expression for the solution of estimating equations. The iterative methods make use of the initial values of the parameters. We have used the search algorithm for performing the optimization to find the final solutions of MLEE. The proposed approach starts with all possible pairs of doses from the doses considered in the experiment. It then chooses the pair giving the optimum value of a criterion function and the corresponding exact solutions for the parameters based on two observations in the pair as the initial values of parameters for solving MLEE for all observations. The proposed methods are transparent in the selection of the initial values of parameters. The proposed methods are computer intensive like bootstrap and jackknife methods popular among statisticians. We illustrate our two methods of finding the initial values with an observed beetle mortality data. We then apply them to obtain the final solutions using two criterion functions. We observe that the numerical values of E D 50 for the initial values of the parameters obtained by our approach are almost the same as the numerical values of E D 50 for the final solutions. This closeness of the estimated E D 50 values from our initial parameter values to the estimated E D 50 values from the final solutions is a strong feature of our proposed methods. Moreover, the proposed methods compare favorably with SAS and R in terms of CPU time values.
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- 2010
32. Differential expression of peroxiredoxins in prostate cancer: Consistent upregulation of PRDX3 and PRDX4
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Heather Rojas, Carlos A. Casiano, Hiya Banerjee, Marino De Leon, Sourav Roy, Zhenyu Jia, Anamika Basu, Shannalee R. Martinez, and Michael B. Lilly
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Male ,PCA3 ,Pathology ,medicine.medical_specialty ,Peroxiredoxin III ,Microarray ,Urology ,Adenocarcinoma ,urologic and male genital diseases ,Article ,Prostate cancer ,Prostate ,Cell Line, Tumor ,Biomarkers, Tumor ,medicine ,Humans ,RNA, Messenger ,Aged ,Oligonucleotide Array Sequence Analysis ,Tissue microarray ,business.industry ,Prostatic Neoplasms ,Cancer ,Peroxiredoxins ,Prostate-Specific Antigen ,medicine.disease ,Immunohistochemistry ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Prostate-specific antigen ,medicine.anatomical_structure ,Oncology ,Tissue Array Analysis ,Cancer research ,business - Abstract
BACKGROUND. The peroxiredoxins (PRDXs) are emerging as regulators of antioxidant defense, apoptosis, and therapy resistance in cancer. Because their significance in prostate cancer (PCa) is unclear, we investigated their expression and clinical associations in PCa. METHODS. Transcript expression of PRDX1–6 in PCa was evaluated in cancer gene microarray datasets, whereas protein expression was evaluated by immunoblotting in prostate cell lines, and by immunohistochemistry (IHC) in prostate tissue microarrays (TMAs) containing tumor (n ¼ 80) and control (n ¼ 17) tissues. PRDX3 was also analyzed in TMAs containing PCa tissues from African-American and Caucasian patients (n ¼ 150 per group). PRDX expression was correlated with patients’ clinicopathologic characteristics. RESULTS. Analysis of PRDX expression in cancer microarray datasets revealed consistent upregulation (tumor vs. normal) of PRDX3 and 4. All PRDXs exhibited elevated protein expression in PCa cell lines, compared with non-tumor cells. IHC revealed significant overexpression of PRDX3 and 4 in PCa, associated with age, increased prostate specific antigen (PSA), tumor stage, or Gleason score. High PRDX3 staining was associated with early age and elevated Gleason score at time of radical prostatectomy in African-American but not in Caucasian patients with PCa. PSA recurrence free survival in patients with low PRDX3 tumor expression was significantly longer in Caucasians compared to African-Americans, but no difference was detected for high expression. CONCLUSIONS. PRDXs exhibit differential expression in prostate tumors, with PRDX3 and 4 consistently upregulated. Their role in PCa development, and their potential as biological determinants of PCa health disparities and novel therapeutic targets, deserve further investigation. Prostate 71: 755–765, 2011. # 2010 Wiley-Liss, Inc.
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- 2010
33. Role of ofatumumab (OFA) maintenance treatment in relapsed chronic lymphocytic leukemia (CLL): Final analysis of PROLONG study
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Sebastian Grosicki, Marinus H. J. van Oers, Lukas Smolej, Tommaso Stefanelli, Mario Petrini, Mark-David Levin, Jaclyn Davis, Fritz Offner, Petra Hoever, Hiya Banerjee, and Christian H. Geisler
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Phases of clinical research ,Relapsed chronic lymphocytic leukemia ,Interim analysis ,Ofatumumab ,030226 pharmacology & pharmacy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Internal medicine ,medicine ,In patient ,030212 general & internal medicine ,Progression-free survival ,business ,neoplasms - Abstract
7517Background: An interim analysis of the PROLONG phase 3 study in patients (pts) with CLL showed a significant increase in progression free survival (PFS) with OFA maintenance without unexpected ...
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- 2018
34. LEDGF/p75 Overexpression Attenuates Oxidative Stress-Induced Necrosis and Upregulates the Oxidoreductase ERP57/PDIA3/GRP58 in Prostate Cancer
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Hiya Banerjee, Leslimar Rios-Colon, Shannalee R. Martinez, Tracy R. Daniels-Wells, Lai Sum Leoh, Melanie Mediavilla-Varela, Carlos A. Casiano, Christina K. Cajigas-Du Ross, Stephanny Acevedo-Martinez, Anamika Basu, and Heather Rojas
- Subjects
0301 basic medicine ,Male ,Transcriptional Activation ,Programmed cell death ,Protein Disulfide-Isomerases ,lcsh:Medicine ,Apoptosis ,PDIA3 ,Biology ,Inhibitor of apoptosis ,03 medical and health sciences ,Transactivation ,Necrosis ,Downregulation and upregulation ,Cell Line, Tumor ,Humans ,lcsh:Science ,Tumor microenvironment ,Multidisciplinary ,lcsh:R ,Prostatic Neoplasms ,Molecular biology ,3. Good health ,Oxidative Stress ,030104 developmental biology ,Intercellular Signaling Peptides and Proteins ,lcsh:Q ,Chromatin immunoprecipitation ,Research Article - Abstract
Prostate cancer (PCa) mortality is driven by highly aggressive tumors characterized by metastasis and resistance to therapy, and this aggressiveness is mediated by numerous factors, including activation of stress survival pathways in the pro-inflammatory tumor microenvironment. LEDGF/p75, also known as the DFS70 autoantigen, is a stress transcription co-activator implicated in cancer, HIV-AIDS, and autoimmunity. This protein is targeted by autoantibodies in certain subsets of patients with PCa and inflammatory conditions, as well as in some apparently healthy individuals. LEDGF/p75 is overexpressed in PCa and other cancers, and promotes resistance to chemotherapy-induced cell death via the transactivation of survival proteins. We report in this study that overexpression of LEDGF/p75 in PCa cells attenuates oxidative stress-induced necrosis but not staurosporine-induced apoptosis. This finding was consistent with the observation that while LEDGF/p75 was robustly cleaved in apoptotic cells into a p65 fragment that lacks stress survival activity, it remained relatively intact in necrotic cells. Overexpression of LEDGF/p75 in PCa cells led to the upregulation of transcript and protein levels of the thiol-oxidoreductase ERp57 (also known as GRP58 and PDIA3), whereas its depletion led to ERp57 transcript downregulation. Chromatin immunoprecipitation and transcription reporter assays showed LEDGF/p75 binding to and transactivating the ERp57 promoter, respectively. Immunohistochemical analysis revealed significantly elevated co-expression of these two proteins in clinical prostate tumor tissues. Our results suggest that LEDGF/p75 is not an inhibitor of apoptosis but rather an antagonist of oxidative stress-induced necrosis, and that its overexpression in PCa leads to ERp57 upregulation. These findings are of significance in clarifying the role of the LEDGF/p75 stress survival pathway in PCa.
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- 2015
35. Pazopanib exposure-response assessment as adjuvant therapy for patients with localized or locally advanced renal cell carcinoma (RCC) following nephrectomy
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Maurizio Voi, Paul Russo, Cora N. Sternberg, Paola Aimone, Naomi B. Haas, Hiya Banerjee, Robert J. Motzer, Christian Doehn, Frede Donskov, and Mohamed Elmeliegy
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Locally advanced ,Urology ,medicine.disease ,Nephrectomy ,Pazopanib ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Renal cell carcinoma ,030220 oncology & carcinogenesis ,medicine ,Adjuvant therapy ,business ,Adjuvant ,Exposure response ,medicine.drug - Abstract
4564 Background: PROTECT was a Phase 3 randomized placebo-controlled study to evaluate pazopanib efficacy and safety as adjuvant RCC treatment. The starting dose was 800 mg daily, which was reduced to 600 mg in an attempt to improve tolerability. Pazopanib trough concentrations (Ctrough) were collected from 358 patients at the 600-mg starting dose at two timepoints (Week 3/ 5 and Week 16/20). This analysis characterized the relationship between Ctrough and efficacy and safety endpoints. Methods: The relationship between pazopanib Ctrough and disease-free survival (DFS) was explored by Cox regression analysis. DFS of pazopanib Ctrough quartiles was explored using Kaplan-Meier plots. Exposure-safety relationship was explored via summaries of all grade adverse events (AEs), grade 3/4 (G3/4) AEs, and AE-related treatment discontinuation by Ctrough quartiles. Results: The geometric mean (geo-CV%) of Ctrough at 600-mg dose was 31.4 (57%) µg/mL and 25.3 (70%) µg/mL for Week 3/5 and Week 16/20, respectively. At Week 16/20, Ctrough values overlapped among patients receiving 400-, 600-, and 800-mg doses. Cox regression analysis showed pazopanib Ctrough at Week 3/5 as a significant covariate for DFS after adjusting for TNM staging and Fuhrman Nuclear grading (HR: 0.58, 95% CI, 0.42, 0.82; p = 0.002). Longer DFS was observed in higher Week 3/5 Ctrough quartiles (median DFS by quartile—Q1: 41.89 months, Q2-Q4: median DFS not reached). Incidence of all-grade AEs, as well as G3/4 hypertension, increased as Ctrough increased. Treatment discontinuation due to hypertension among pazopanib-treated subjects was low (3.1% vs < 1% in the placebo group). Ctrough was not correlated to G3/4 ALT increase. Incidence of other G3/4 AEs plateaued at higher Ctrough. No relationship was observed between Ctrough and treatment discontinuation due to AEs. Conclusions: Pazopanib Ctrough levels in PROTECT were consistent with levels associated with efficacy in the advanced setting. Higher pazopanib Ctrough correlated with longer DFS. Higher pazopanib exposure did not increase the incidence of G3/4 AEs, with the exception of hypertension, which was adequately controlled and managed. Clinical trial information: NCT01235962.
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- 2017
36. Depression severity in electroconvulsive therapy (ECT) versus pharmacotherapy trials
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Rebecca G. Knapp, Mimi C. Briggs, Charles H. Kellner, Rachael J. Shapiro, Hiya Banerjee, Lauren S. Liebman, Rosa M. Pasculli, Gabriella M. Ahle, Dennis M. Popeo, and David C. Kaicher
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Psychiatric Status Rating Scales ,medicine.medical_specialty ,business.industry ,Depression ,medicine.medical_treatment ,Neuroscience (miscellaneous) ,MEDLINE ,Hamilton Rating Scale for Depression ,medicine.disease ,behavioral disciplines and activities ,Clinical trial ,Psychiatry and Mental health ,Electroconvulsive therapy ,Pharmacotherapy ,Treatment Outcome ,Mood disorders ,Sample size determination ,Internal medicine ,mental disorders ,medicine ,Humans ,business ,Psychiatry ,Electroconvulsive Therapy ,Depression (differential diagnoses) - Abstract
Objective We sought to compare the level of severity of depressive symptoms on entry into electroconvulsive therapy (ECT) clinical trials versus pharmacotherapy clinical trials. Data sources English-language MEDLINE/PubMed publication databases were searched for ECT literature (search terms: ECT, electroconvulsive therapy, depression, and Hamilton) for clinical trials in which depressed patients had baseline Hamilton Rating Scale for Depression (HRSD) scores. For comparison, we used a convenience sample of 7 large pharmacotherapy trials in major depression (N = 3677). The search included articles from 1960 to 2011. Study selection We included 100 studies that met the following criteria: ECT trial for depression, patients adequately characterized by diagnosis at baseline, and patients rated at baseline by 15-item HRSD (HRSD15), HRSD17, HRSD21, HRSD24, or HRSD28, with mean (SD) and sample size (n) reported. For the comparator pharmacotherapy trials, we chose to use a subset of the studies (excluding one study of minor depression) in the widely publicized meta-analysis of Fournier et al, as well as the STAR*D study and one additional study by Shelton et al. This provided 7 studies of major depression using HRSD17 (total N = 3677). Data extraction Data extracted included number of subjects and baseline and final HRSD scores, with mean (SD) values. Results Of 100 ECT studies, 56 studies (N = 2243) used the HRSD17 version. The mean baseline HRSD17 score in the ECT trials was 27.6, the mean in the pharmacotherapy trials was 21.94, a statistically, and clinically, significant difference. In a subanalysis of the 16 ECT studies that used the HRSD24 version, the mean baseline score was 32.2. Conclusions This selective literature review confirms that patients who entered ECT clinical trials were more severely ill than those who entered the selected comparator pharmacotherapy trials. Such data highlight the critical role of ECT in the treatment of severe and treatment-resistant mood disorders.
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- 2014
37. Cotinine levels among betel quid users and cigarette smokers in Cambodia
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Hiya Banerjee, Jayakaran S. Job, Sothy Khieng, Zuhair S. Natto, Daravuth Yel, Pramil N. Singh, and Rituraj Saxena
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Adult ,Male ,Rural Population ,media_common.quotation_subject ,Article ,chemistry.chemical_compound ,Young Adult ,Cigarette smoking ,Tobacco users ,Surveys and Questionnaires ,Medicine ,Humans ,Cotinine ,Saliva ,Areca ,media_common ,Aged ,Aged, 80 and over ,Traditional medicine ,business.industry ,Addiction ,Smoking ,Public Health, Environmental and Occupational Health ,Middle Aged ,Confidence interval ,Smokeless tobacco ,chemistry ,Female ,Habit ,Betel quid ,business ,Cambodia ,Demography - Abstract
Smokeless tobacco use in the form of the betel quid is common in the Western Pacific Region, and yet few studies have determined the nicotine delivery of this habit. During a validation substudy, we randomly sampled 201 adults from a rural province of Cambodia and determined nonparametric (bootstrapped) confidence intervals (CIs) for salivary cotinine levels in tobacco users. We found that cotinine levels for daily betel quid use among women (95% CI = 218.6-350.0 ng/mL) were (1) similar to the levels for daily cigarette smoking in men (95% CI = 240.2-317.1 ng/mL) and (2) significantly higher than the levels for daily cigarette smoking in women (95% CI = 71.8-202.7 ng/mL). The 95% confidence range for these habits exceeded the threshold for addiction. Our findings from rural Cambodia indicate that the typical betel quid habit among women supports the same level of nicotine addiction as the typical cigarette habit in men.
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- 2013
38. Sensitivity, specificity, and utility of locomotor activity data generated with the kinder motor monitor system in neurotoxicity safety assessment
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Mark A. Osinski, Jacqueline A. Walisser, Brittney Epping, Christopher Elders, Christopher L. Douglas, and Hiya Banerjee
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Pharmacology ,business.industry ,Neurotoxicity ,medicine ,Sensitivity (control systems) ,Toxicology ,medicine.disease ,business ,Neuroscience ,Locomotor activity ,Simulation - Published
- 2013
39. Abstract 3117: Overexpression of the stress transcription co-activator LEDGF/p75 contributes to the upregulation of the stress protective genes HSP27, ERp57 and CYGB in prostate cancer
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Laisum Leoh, Melanie Mediavilla-Varela, Hiya Banerjee, Carlos A. Casiano, Christina Cajigas, Benanette Medina, Anamika Basu, and Heather Rojas
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Cancer Research ,Cytoglobin ,Biology ,medicine.disease ,Prostate cancer ,Oncology ,Hsp27 ,Downregulation and upregulation ,Transcription (biology) ,Cancer research ,medicine ,biology.protein ,Gene ,Co activator - Abstract
Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer related death in men in the US. PCa tumor aggressiveness, response to treatment, and mortality are worst in African-American men, compared to other ethnic groups, thus presenting a major health disparity. Our group reported previously that lens epithelium derived growth factor p75 (LEDGF/p75), a stress survival transcription coactivator, has elevated expression in PCa cells and tissues and promotes resistance to cell death induced by oxidative stress and chemotherapy. This is likely due to its ability to transactivate promoter regions of stress and antioxidant genes such as peroxiredoxin 6 (Prdx6) and heat shock protein 27 (HSP27). We hypothesized that high expression of LEDGF/p75 in prostate tumor cells and tissues contributes to the elevated expression of its putative target genes, some of which were identified in previous studies by our group and others. These include genes associated with stress protection and chemotherapy resistance such as HSP27, endoplasmic reticulum protein 57 (ERp57), and cytoglobin (CYGB). To test this hypothesis we performed an expression analysis of LEDGF/p75, HSP27, ERp57 and CYGB proteins in human PCa cell lines using immunoblotting, and in prostate tumor tissues using immunohistochemistry on tumor tissue microarrays (TMAs). PCa cell lines included stable PC3 clones overexpressing LEDGF/p75, as well as docetaxel (DTX) resistant PC3-DR and DU145-DR cells overexpressing this protein, with their corresponding parental DTX sensitive cell lines. The TMAs contained tissue specimens corresponding to prostate tumor, hyperplasia, normal-adjacent, and disease-free normal prostate tissues. Correlations between the expression of LEDGF/p75 and HSP27 or ERp57 or CYGB in cell lines as well as in tumors and normal tissues was determined. Our results indicated that overexpression of LEDGF/p75 in PC3 stable clones and in DTX resistant PCa cells was associated with increased protein expression of HSP27, ERp57 and CYGB. Statistically significant correlation was also observed between the protein levels of LEDGF/p75 and HSPp27 or ERp57 or CYGB in the TMAs. Luciferase-based transcription reporter assays confirmed that the promoter regions of HSP27 and ERp57 are activated by LEDGF/p75 in PCa cells. Chromatin immunoprecipitation assays also demonstrated binding of LEDGF/p75 to HSP27 promoter in PCa cells. Additional promoter activation studies are in progress to demonstrate that LEDGF/p75 transcriptionally regulates ERp57 and CYGB genes. These results enhance our understanding of the contribution of LEDGF/p75 overexpression to the activation of stress protective genes and its implications for chemotherapy resistance in metastatic PCa. Citation Format: Anamika Basu, Christina Cajigas, Benanette Medina, Heather Rojas, Hiya Banerjee, Melanie Mediavilla-Varela, Laisum Leoh, Carlos Casiano. Overexpression of the stress transcription co-activator LEDGF/p75 contributes to the upregulation of the stress protective genes HSP27, ERp57 and CYGB in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3117. doi:10.1158/1538-7445.AM2013-3117
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- 2013
40. Expression of the Stress Response Oncoprotein LEDGF/p75 in Human Cancer: A Study of 21 Tumor Types
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Kayla Y. Perez, Anamika Basu, Irena B. Cabrera, Marino De Leon, Carlos A. Casiano, Hiya Banerjee, and Heather Rojas
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Male ,Proteomics ,Histology ,lcsh:Medicine ,Biology ,medicine.disease_cause ,Polymerase Chain Reaction ,Molecular Genetics ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Downregulation and upregulation ,RNA interference ,Cell Line, Tumor ,Neoplasms ,Molecular Cell Biology ,Genetics ,medicine ,Animals ,Humans ,lcsh:Science ,Oligonucleotide Array Sequence Analysis ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Tissue microarray ,Cancer Risk Factors ,lcsh:R ,Computational Biology ,medicine.disease ,Immunohistochemistry ,Molecular biology ,Rats ,3. Good health ,Real-time polymerase chain reaction ,Oncology ,030220 oncology & carcinogenesis ,Intercellular Signaling Peptides and Proteins ,Medicine ,lcsh:Q ,Female ,RNA Interference ,DNA microarray ,Carcinogenesis ,Research Article - Abstract
Oxidative stress-modulated signaling pathways have been implicated in carcinogenesis and therapy resistance. The lens epithelium derived growth factor p75 (LEDGF/p75) is a transcription co-activator that promotes resistance to stress-induced cell death. This protein has been implicated in inflammatory and autoimmune conditions, HIV-AIDS, and cancer. Although LEDGF/p75 is emerging as a stress survival oncoprotein, there is scarce information on its expression in human tumors. The present study was performed to evaluate its expression in a comprehensive panel of human cancers. Transcript expression was examined in the Oncomine cancer gene microarray database and in a TissueScan Cancer Survey Panel quantitative polymerase chain reaction (Q-PCR) array. Protein expression was assessed by immunohistochemistry (IHC) in cancer tissue microarrays (TMAs) containing 1735 tissues representing single or replicate cores from 1220 individual cases (985 tumor and 235 normal tissues). A total of 21 major cancer types were analyzed. Analysis of LEDGF/p75 transcript expression in Oncomine datasets revealed significant upregulation (tumor vs. normal) in 15 out of 17 tumor types. The TissueScan Cancer Q-PCR array revealed significantly elevated LEDGF/p75 transcript expression in prostate, colon, thyroid, and breast cancers. IHC analysis of TMAs revealed significant increased levels of LEDGF/p75 protein in prostate, colon, thyroid, liver and uterine tumors, relative to corresponding normal tissues. Elevated transcript or protein expression of LEDGF/p75 was observed in several tumor types. These results further establish LEDGF/p75 as a cancer-related protein, and provide a rationale for ongoing studies aimed at understanding the clinical significance of its expression in specific human cancers.
- Published
- 2012
41. Abstract A108: Differential expression of peroxiredoxins in prostate cancer: Ethnic differences in the association of PRDX3 expression with clinical outcomes
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Heather Rojas, Michael B. Lilly, Melanie Mediavilla-Varela, Dan Mercola, Anamika Basu, Roy Sourav, Hiya Banerjee, Carlos A. Casiano, Zhenyu Jia, Shannalee R. Martinez, and Marino De Leon
- Subjects
PCA3 ,Oncology ,medicine.medical_specialty ,Tissue microarray ,Microarray ,Epidemiology ,business.industry ,Cancer ,medicine.disease ,Malignant transformation ,Prostate-specific antigen ,Prostate cancer ,medicine.anatomical_structure ,Prostate ,Internal medicine ,Immunology ,Medicine ,business - Abstract
Prostate cancer (PCa) is the most frequently diagnosed male cancer and the second leading cause of cancer death in men in the United States. This growing public health challenge is aggravated by disparities in the incidence and mortality of PCa among African-American (AA) men, compared to Caucasian (CC) men and other ethnic groups. The reasons for these disparities are not completely understood, although available evidence points to the convergence of multiple, interrelated factors, such as socioeconomics, unequal access to health care and screening, unhealthy lifestyle and diet, ancestry, and genetic susceptibility. Emerging evidence suggests that chronic inflammation of the prostate contributes to PCa development by inducing oxidative molecular damage, which in turns lead to the upregulation of stress and redox proteins that protect tumor cells against apoptosis and therapeutic interventions. Evaluation of the expression and role of these proteins in prostate tumors from different ethnic populations would help define molecular and cellular factors associated with prostate tumor aggressiveness and therapy resistance, and uncover potential biological determinants of PCa health disparities. The peroxiredoxin (PRDX) protein family consists of six anti-oxidant enzymes (PRDX1-6) that are emerging as key regulators of cellular anti-oxidant defense, and are being increasingly implicated in malignant transformation and therapy resistance. Very little is known about their role in prostate cancer. In this study we investigated their expression and association with clinical outcomes in prostate cancer (PCa). The expression of PRDX1-6 in PCa was evaluated in 14 cancer gene microarray datasets (from Oncomine and SPECS), by immunoblotting in a panel of 11 prostate cell lines, and by immunohistochemistry (IHC) in prostate tissue microarrays (TMA) containing tumor (n=80) and control (n=17) tissues. PRDX3 was also analyzed in TMA containing PCa tissues from AA and CC patients (n=150 per group). PRDX expression was correlated with patients’ clinicopathologic characteristics. Analysis of PRDX expression in cancer microarray databases revealed consistent upregulation (tumor vs normal) of PRDX3 and 4. All PRDXs exhibited elevated protein expression in PCa cell lines, compared with non-tumor cells. IHC revealed significant overexpression of PRDX3 and 4 in PCa, associated with increased prostate specific antigen (PSA), tumor stage, or Gleason score. High PRDX3 expression was associated with early age and elevated Gleason score at time of radical prostatectomy in AA but not in CC patients with PCa. PSA recurrence free survival in patients with low PRDX3 tumor expression was significantly longer in CC compared to AA patients, but no difference was detected for high expression. We conclude that PRDXs exhibit differential expression in prostate tumors, with PRDX3 and 4 consistently upregulated. The role of these two proteins in PCa development, and their potential as biological determinants of PCa health disparities and novel therapeutic targets, deserve further investigation. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A108.
- Published
- 2010
42. Abstract 4667: Elevated expression of the stress oncoprotein LEDGF/p75 in major human cancers
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Anamika Basu, Irena B. Cabrera, Hiya Banerjee, Marino De Leon, Carlos A. Casiano, Heather Rojas, and Kayla Y. Perez
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Programmed cell death ,Tissue microarray ,biology ,Cancer ,Inflammation ,medicine.disease ,Staining ,medicine.anatomical_structure ,Oncology ,Prostate ,medicine ,biology.protein ,Immunohistochemistry ,Antibody ,medicine.symptom - Abstract
Long-term cumulative exposure to environmental factors (i.e., dietary habits, unhealthy lifestyle, infectious agents, etc) lead to chronic inflammation and an augmented state of cellular oxidative stress, which contribute to the etiology and progression of various human cancers. We reported previously that lens epithelium derived growth factor p75 (LEDGF/p75), a transcription coactivator, has an elevated expression in human prostate tumors and cell lines. We hypothesize that LEDGF/p75 might be highly expressed in tissues with elevated oxidative stress such as tumors, because of its ability to transcriptionally activate stress genes that promote resistance to stress- and chemotherapy-induced cell death. To date, there have not been any comprehensive studies aimed at investigating the expression of LEDGF/p75 in human cancers. We performed an expression analysis of LEDGF/p75 protein in a panel of human cancers using immunohistochemistry on commercially available tissue microarrays (TMAs). Paraffin embedded tissue specimens were deparaffinized, rehydrated and stained with either a rabbit anti-LEDGF/p75 serum or the rabbit pre-immune serum as an antibody control, using a Biogenic i6000 auto stainer (Biogenex Corp.). Images were acquired using an Olympus BX50 microscope equipped with a Spot RT3TM camera. The TMA slides were assessed for LEDGF/p75 immunoreactivity by a pathologist who was blinded for the tumor/normal status of the tissues. A 4-tier grading system (0-negative, 1-weak, 2-moderate and 3-strong staining intensity) was used to evaluate the staining intensity. Associations between LEDGF/p75 expression in tumors and normal tissues were analyzed using Kruskall Wallis's rank sum test. We used TMAs (Imgenex and NDRI) containing specimens corresponding to over 20 major tumor types and normal adjacent tissues. Our data revealed high expression of this protein in tumors of prostate, pancreas, lungs, liver, thyroid, colon, breast and kidney, as compared to corresponding normal adjacent tissues. To further validate our findings, we analyzed LEDGF/p75 expression in the above-mentioned cancers using TMAs (US BIOMAX), each containing multiple tissues specimens of a specific major tumor type, as well as non-cancerous inflammatory disease and normal post-mortem control tissues. Immunohistochemical analysis revealed high expression of LEDGF/p75 in most of the tumor sections as compared to normal control tissues. The normal tissues showed minimal or no staining. The anti-LEDGF/p75 staining was mostly confined to the nucleus, although cytoplasmic staining was also evident in many cells. These results further validate the high expression of LEDGF/p75 in major human cancers and constitute the first step towards defining the biological significance of LEDGF/p75 expression in human cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4667.
- Published
- 2010
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